Ethyl Acetate → N6-Methyl-4-(4-amino-3-chlorophenoxy)-7-(benzyloxy)-6-quinolinecarboxamide

HRID 388037Notes

Reaction equation

HRID 388037 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[Cl:9].[H-].[Na+].[CH3:12][NH:13][C:14]([C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[N:22]=[CH:21][CH:20]=[C:19]2Cl)=[O:15].C(OCC)(=O)C>CS(C)=O.O>[CH3:12][NH:13][C:14]([C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[N:22]=[CH:21][CH:20]=[C:19]2[O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([Cl:9])[CH:4]=1)=[O:15]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 871844-Amino-3-chlorophenolHCID 22936745N6-Methyl-7-(benzyloxy)-4-chloro-6-quinolinecarboxamide

Product 1

HCID 22936337N6-Methyl-4-(4-amino-3-chlorophenoxy)-7-(benzyloxy)-6-quinolinecarboxamideYield 87.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

After dissolving 4-amino-3-chlorophenol (624 mg, 4.35 mmol) in dimethylsulfoxide (15 ml), sodium hydride (174 mg, 4.35 mmol) was gradually added at room temperature and the mixture was stirred for 30 minutes. N6-Methyl-7-(benzyloxy)-4-chloro-6-quinolinecarboxamide (947 mg, 2.90 mmol) was added, and the mixture was heated at 100° C. while stirring for 2 hours. After cooling to room temperature, the reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with 1N aqueous sodium hydroxide, water and saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was suspended in ethyl acetate, the suspension was diluted with hexane and the crystals were filtered out and blow-dried to obtain the title compound (1.098 g, 2.53 mmol, 87.3%) as light brown crystals.

Workup

  1. additionwas gradually added at room temperature
  2. stirringwhile stirring for 2 hours
  3. temperatureAfter cooling to room temperature
  4. washthe organic layer was washed with 1N aqueous sodium hydroxide, water and saturated saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off
  7. additionthe suspension was diluted with hexane
  8. filtrationthe crystals were filtered out and
  9. customblow-dried

Sources & evidence

ORD record
ord-8176ca3d6df74fc8927937a07cba46e1
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

Loading…